Aashish Manglik

Aashish Manglik, MD, PhD, Distinguished Faculty Fellow, Department of Molecular and Cellular Physiology

Stanford University School of Medicine

 

Research Description: Dr. Manglik is the inaugural Distinguished Faculty Fellow at Stanford University School of Medicine. He trained with the Nobel Laureate Dr. Brian Kobilka and now heads a group as an independent research position with PI status. The goal of his research program is to understand cellular signaling and how it relates to human physiology and diseases including diabetes mellitus. As part of this program, he has examined the largest class of transmembrane receptors in the human genome, the G protein-coupled receptors (GPCR) using a combination of protein biochemistry, structural biology, biophysics, pharmacology, and protein engineering. These studies have elucidated the molecular mechanisms of adrenergic, muscarinic, and opioid receptor function and have laid important groundwork in the role of protein structural plasticity in GPCR function. Additionally, he is developing new tools to interrogate transmembrane protein signaling. Using these powerful tools, he is currently examining poorly understood transmembrane receptors important in human physiology, including (1) the structural and biophysical basis of function for the iron efflux transporter ferroportin and its regulation by the protein hormone hepcidin and (2) the Neuromedin U receptors implicated by prior studies to regulate insulin and glucagon output by pancreatic islets. The latter study is an active collaboration between the Manglik and Kim labs.

Selected relevant publications (Stanford DRC Members in BOLD):

1.         Manglik A*, Lin H*, Aryal D*, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hubner H, Huang XP, Sassano MF, Giguere P, Lober S, Duan D, Scherrer G, Kobilka BK, Gmeiner P, Roth BL, Shoichet BK. Structure based discovery of opioid analgesics with reduced side effects. Nature. In press.

2.         Manglik A*, Kim TH*, Masureel M, Altenbach C, Yang Z, Hilger D, Lerch MT, Kobilka TS, Thian FS, Hubbell WL, Prosser RS, Kobilka BK. Structural Insights into the Dynamic Process of β2-Adrenergic Receptor Signaling. Cell. 161(5):1101-11 (2015)

3.         Huang W*, Manglik A*#, Venkatakrishnan AJ, Laeremans T, Feinberg EN, Sanborn AL, Kato HE, Livingston KE, Thorsen TS, Kling R, Granier S, Gmeiner P, Husbands SM, Traynor JR, Weis WI, Steyaert J, Dror RO, Kobilka BK#. Structural insights into μ-opioid receptor activation. Nature. 524(7565):315-21 (2015); #Corresponding Author

4.         Manglik A, Kobilka BK. The role of protein dynamics in GPCR function: insights from the β2AR and rhodopsin. Current Opinion in Cell Biology. 27C:136-143 (2014).

5.         Manglik A, Kruse AC, Kobilka TS, Thian FS, Mathiesen JM, Sunahara RK, Pardo L, Weis WI, Kobilka BK, Granier S. Crystal structure of the µ-opioid receptor bound to a morphinan antagonist. Nature. 485(7398): 321-6 (2012).

6.         Shukla AK*, Manglik A*, Kruse AC*, Xiao K, Reis RI, Tseng WC, Staus DP, Hilger D, Uysal S, Huang LY, Paduch M, Tripathi-Shukla P, Koide A, Koide S, Weis WI, Kossiakoff AA, Kobilka BK, Lefkowitz RJ. Structure of active β-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide. Nature. 497(7447):137-41 (2013).

7.         Ring AM*, Manglik A*, Kruse AC*, Enos MD, Weis WI, Garcia KC, Kobilka BK. Adrenaline-activated structure of β2-adrenoceptor stabilized by an engineered nanobody. Nature. (2013)

8.         Granier S, Manglik A*, Kruse AC*, Kobilka TS, Thian FS, Weis WI, Kobilka BK. Structure of the δ-opioid receptor bound to naltrindole. Nature. 485(7398): 400-4 (2012)